The recessive allele for resistance at the Fv-2 locus in mice confers a near-absolute resistance to the erythroleukemia induced by Friend virus. Recent studies have indicated that this allele may be a lethal gene in mice in the absence of another dominant gene which protects the mouse from the lethality. We propose to confirm this preliminary finding, which constitutes the first evidence for an effect of Fv-2 in the absence of virus infection, by a breeding program designed to define and map the "protector" gene and to produce a strain, D2.Fv-2r, congenic with DBA/2 but possessing the Fv-2 resistance plus the protector function. The timing and mechanism of this lethality will also be studied, as will also the hypothesis that an antigen specifically induced by the SFFV component of Friend virus might be related to an antigen of hemopoietic cells governed by the Fv-2s allele. Studies designated to identify new genes capable of conferring resistance to Friend virus disease are also proposed.